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Serum dickkopf-1 in men with advanced prostate cancer.

Sub-category: Tumor & cell biology
Category: Biology of Prostate Cancer
Meeting: 2007 Prostate Cancer Symposium


Abstract No: 67
Author(s): D. A. Bradley, C. Hall, S. Daignault, J. Friedman, K. Ignatoski, J. Escara-Wilke, D. C. Smith, E. T. Keller
Abstract: Introduction: The Wnt signaling pathway and its key player, B-catenin have recently been implicated in the development and progression of prostate cancer (PCa). Wnt activity is antagonized by endogenous proteins including dickkopf-1 (DKK-1). We have demonstrated that DKK-1 modulates the ability of PCa cells to promote bone osteoblastic activity in a murine model. Therefore, we hypothesize that DKK-1 modulates osteoblastic lesions in men with PCa. DKK-1 has never been measured from human serum. We therefore investigated whether DKK-1 could be measured from serum in men with metastatic hormone refractory prostate cancer (HRPCa). Methods: Utilizing blood samples from men with HRPCa and bone metastasis who were enrolled in a prospective, randomized trial and treated with zoledronic acid (Z) or estramustine/docetaxel (ED) for the first cycle and combination ZED for all subsequent cycles, we examined whether DKK-1 could be measured in serum. We then investigated whether serum DKK-1 levels were affected by therapy and whether there was a correlation between treatment response and change in DKK-1 levels. DKK-1 was quantified from serum samples utilizing a sandwich ELISA developed in our laboratory from a DKK-1 Duoset ELISA development kit (R&D Systems, Inc, Minneapolis, MN). Results: We successfully quantified DKK-1 serum levels from 13 men on the Z arm and 14 men on the ED arm. Baseline serum levels of DKK-1 were 98-1,650 pg/ml. No significant difference was seen between baseline and post cycle 1 serum DKK-1 levels in the Z arm (p = 0.8466) or the ED arm (p = 0.4592). In an exploratory analysis, no significant difference in the relative difference of quantitative serum DKK-1 was seen between responders and nonresponders as determined by a 50% decrease in PSA after 3 cycles of therapy (p = 0.8062). Conclusions: DKK-1 can be measured from serum in men with metastatic HRPCa and confirmed bone metastasis; however, it does not appear to be prognostic for therapeutic response. The small sample size may have not provided enough power to determine a significant difference. Based on preclinical observations, further investigation into the role of DKK-1 in prostate cancer metastasis is warranted.

(courtesy rdh19869 : http://tinyurl.com/2rwopq )